Availability of in vitro cell selective system will greatly facilitate the understanding of many genetic disorders. Unfortunately, such selective systems are very limited for mammalian cells. We have now developed a selection system for cystinotic cells. These cells due to an unknown genetic and biochmical disorder accumulate cystine in their lysosomes causing the disease, cystinosis. We found that extracellular cysteine concentrations between 0.5 and 2.5mN resulted in death of normal but not cystinotic fibroblasts grown in Eagle's Minimal Essential Medium (MEX) containing supplemental fetal calf serum and antibiotic. In co-cultivation experiments of N3-thymidine labelled cystinotic and nonradioactive normal cells, autoradiography confirmed the selective survival of cystinotic cells in medium containing 1mN cysteine. At this concentration of 1mN cysteine, intracellular cysteine content increased slightly in survivingnormal but not cystinotic cells. This resistance of cystinotic fibroblasts to elevated extracellular cysteine forms the basis for an in vitro selective system for these mutant cells.